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Xiaohua Gong, Jing Zeng, Catherine Cheng, Chun-hong Xia; The role of periaxin genetic variances in cataract formation of Gja3 knockout mice. Invest. Ophthalmol. Vis. Sci. 2013;54(15):1263.
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To identify a candidate gene on mouse chromosome 7 that acts as a co-dominant genetic modifier to control the severity of cataracts in Gja3 knockout mice between C57/B6J (B6) and 129SvJae (129) mouse strain backgrounds, and to test a hypothesis that periaxin is the genetic modifier in cataractogenesis by regulating the membrane/cytoskeleton functions in lens fiber cells.
Cataract severity was evaluated by slit-lamp examination in vivo and quantified by measuring lens light scattering in vitro. SNPs identification was used to determine candidate genes for this genetic modifier. RT-PCR, western blotting and immunohistochemistry were performed to evaluate candidate genes and to elucidate their molecular and cellular changes in cataract formation and membrane/cytoskeleton structures in the lens.
SNPs data reveal several candidate genes with missense mutations that are utilized in the lens. RT-PCR, western blotting and immunohistochemical data indicate that periaxin (Prx), a scaffold protein of the membrane/cytoskeleton in lens fibers, is a strong candidate for this genetic modifier. Genetic variances show 4 different amino acid residue substitutions in Prx between 129 and B6 mouse strain backgrounds. Prx proteins are stably associated with the membrane/cytoskeleton of mature fiber cells only in 129 lenses, but not in B6 lenses. Cataract inhibition is associated with a rapid disappearance of Prx proteins from the membrane/cytoskeleton of differentiating fiber cells in B6 Gja3 knockout lenses.
Genetic variances of the Prx gene between 129 and B6 mouse strain backgrounds cause functional changes of the Prx protein that are probably related to its role in membrane/cytoskeleton function. Promoting the degradation of Prx in lens fiber cells may be an effective way to inhibit cataract formation. Further studies of the functional domains of Prx will be important to understand its role in lens fiber cells and cataract formation.
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